Previous work has demonstrated that dopamine and estradiol interact in the CNS in the regulation of pituitary gonadotropin secretion. The proposed experiments will attempt to characterize certain aspects of the central interaction of dopamine and estradiol and to elucidate possble mechanisms or subcellular sites of interaction. Effects of selected dopaminergic agonists and antagonists on nuclear estradiol binding in estradiol target areas in CNS will be investigated by measuring total uptake and subcellular distribution of specifically bound estradiol in response to the drugs used. The mechanism of the dopaminergic stimulation of nuclear estradiol uptake observed in our laboratory will be investigated by means of time course studies of estradiol nuclear binding and by measurement of formation and subcellular distribution of catechol estradiol in estradiol target areas of the CNS. An attempt will also be made to determine the subcellular site of action of drugs affecting estradiol binding by means of synaptosomal estradiol uptake studies and studies of nuclear binding of estradiol after nuclear and extranuclear fractions from tissues of animals receiving no pretreatment or treatment with a dopaminergic agonist or antagonist are recombined. Other studies will examine effects of previous endocrine history on the response of estradiol-concetrating neurons to dopaminergic agonists and antagonists in rats of both sexes and in androglen-sterilized female rats, and in rats at different times following gonadectomy. Possible correlations between drug effects on CNS nuclear estradiol binding and gonadotropin-prolactin secretion will also be investigated. All work will be done in the rat.